Lung Immune Tone Regulation by the Gut Microbiome

Lung immune tone refers to the homeostatic set-point driving the inflammatory and host-defense responses within the lung. Individuals with different lung immune tones likely respond to infection and injury very differently resulting in pro- or anti-host (beneficial vs. harmful) responses. Therefore, deciphering the mechanistic regulation of lung immune tone may pave the way towards therapeutic approaches to manipulate it in health and disease.
Factors that regulate organ immune tone have been shown to emanate from the gut microbiota, including short-chain fatty acids (SCFAs), such as propionate and butyrate. We previously demonstrated that these metabolites modify the inflammatory capacity of microbial toxins, such as LPS both positively and negatively depending on the levels present and context within the lung. We linked this activity of SCFAs to their ability to regulate lung immune tone through receptor-mediated signaling and epigenetic mechanisms in vitro and in vivo. The presence of large variability lung tissue levels of SCFAs between patients suggests that gut microbiota regulation of lung immune tone could play a key role in helping understand patient responses to injury and infection. Furthermore, we are exploring the use of dietary interventions to affect gut microbiota composition and gut metabolite-mediated regulation of lung immune tone in vivo.
Overall, the capacity of gut microbiota to influence and even control host immune responses is a topic of intense interest and research. Here we demonstrate the strength of the gut-lung axis as it seeks to promote health or disease based on host dietary choices and resident gut microbiome composition.

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